The program's overall objectives are to bring the latest advances in stroke care immediately into clinical application to all patients and to conduct innovative, high impact clinical research related to understanding human stroke pathophysiology, and to evaluate novel stroke diagnostic and therapeutic strategies using MRI. Stroke is the third leading cause of death, the leading cause of long term disability in the elderly and has a monetary cost to society in excess of 40 billion dollars per year. Only one therapy is approved as a treatment for stroke, the thrombolytic agent tissue plasminogen activator (tPA) administered within three hours of onset, but is only received by 2-5% of stroke patients. We are studying ways to increase and improve the utilization of thrombolytic therapy in acute stroke. We established a stroke center at Suburban Hospital, a 397-bed private community hospital in Bethesda, Maryland, consisting of an emergency response team and inpatient service staffed by neurologists and nurses specializing in stroke and a research infrastructure centered around a state-of-the-art MRI facility. In the last year we treated 16.9% of patients admitted with ischemic stroke with intravenous tPA, well above the national rate of tPA utilization for stroke (generally quoted as 2-5%), demonstrating the success of our center in increasing access to proven therapy. The NIH Stroke Center at Suburban Hospital has become a vital and highly regarded part of the local medical community and a model system for successful implementation of new stroke therapies into the community. Our advanced imaging investigations of these patients treated with tPA have increased our understanding of the brain's response to tPA therapy. An interim analysis of our patients treated to date and studied with diffusion and perfusion weighted MRI indicate that approximately 50% of patients treated with tPA show an improvement in blood flow to the brain two hours after treatment and a long term recovery of brain injury that was evident prior to initiation of therapy. Data collection and analysis is ongoing in our projects to test the relative sensitivity of MRI and computer tomography (CT) in detection of acute hemorrhage and to determine the time course over which cerebral infarction becomes stable and irreversible